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Pathway Description
Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
Medium-chain acyl-CoA dehydrogenase deficiency, which is also known as MCADD, is a rare inherited inborn error of metabolism (IEM) medium-chain fatty acid metabolism. The estimated birth prevalence of MCADD is between 1 in 4 900 to 1 in 27 000 in Caucasian populations and is highest in Northern European individuals. Worldwide birth prevalence is 1 in 14 600. MCADD is an autosomal recessive disorder associated with a mutation in the enzyme medium-chain acyl-CoA dehydrogenase (MCAD). MCAD is an enzyme that catalyzes the initial step in each cycle of medium-chain fatty acid beta-oxidation in the mitochondria of cells. MCAD’s action results in the introduction of a trans-double-bond between C2 and C3 of the acyl-CoA thioester substrate. Defects in MCAD leads to the accumulation of medium-chain fatty acids in the blood, lowering the blood's pH and causing acidosis. Likewise, individuals with MCADD have difficulty metabolizing fats. As a result, MCADD is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain aciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. Intolerance to fasting and hypoglycemia result from the inability to gain energy and make sugar from fat stores, which is how most excess energy from food is stored. It is rare for the signs and symptoms of MCADD to first appear during adulthood. Typically, they manifest during infancy or early childhood and can include lethargy, hypoglycemia, and vomiting. MCAD-deficient individuals are at risk for breathing difficulties, liver problems, seizures, brain damage, coma, and sudden death. Fasting or illnesses (e.g. viral infections) can trigger related problems. Infants and young children with MCADD need to eat frequently to prevent hypoglycemia or a metabolic crisis. MCADD is occasionally mistaken for Reye syndrome, a severe disorder that may manifest in children during apparent recovery from viral infections such as flu or chickenpox. The majority of Reye syndrome cases are associated with aspirin use during these viral infections.
References
Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD) References
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Fatty Acid Metabolism References
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Pubmed: 17242355
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000542
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